Therapeutic assay with the non-toxic c-terminal fragment of tetanus toxin (TTC) in transgenic murine models of prion disease

Betancor, M. (Universidad de Zaragoza) ; Moreno Martínez, L. (Universidad de Zaragoza) ; López-Pérez, Ó. ; Otero, A. (Universidad de Zaragoza) ; Hernaiz, A. (Universidad de Zaragoza) ; Barrio, T. ; Badiola, J.J. (Universidad de Zaragoza) ; Osta, R. (Universidad de Zaragoza) ; Bolea, R. (Universidad de Zaragoza) ; Martín Burriel, I. (Universidad de Zaragoza)

Resumen: The non-toxic C-terminal fragment of the tetanus toxin (TTC) has been described as a neuroprotective molecule since it binds to Trk receptors and activates Trk-dependent signaling, activating neuronal survival pathways and inhibiting apoptosis. Previous in vivo studies have demonstrated the ability of this molecule to increase mice survival, inhibit apoptosis and regulate autophagy in murine models of neurodegenerative diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. Prion diseases are fatal neurodegenerative disorders in which the main pathogenic event is the conversion of the cellular prion protein (PrPC) into an abnormal and misfolded isoform known as PrPSc. These diseases share different pathological features with other neurodegenerative diseases, such as amyotrophic lateral sclerosis, Parkinson’s disease or Alzheimer’s disease. Hitherto, there are no effective therapies to treat prion diseases. Here, we present a pilot study to test the therapeutic potential of TTC to treat prion diseases. C57BL6 wild-type mice and the transgenic mice Tg338, which overexpress PrPC, were intracerebrally inoculated with scrapie prions and then subjected to a treatment consisting of repeated intramuscular injections of TTC. Our results indicate that TTC displays neuroprotective effects in the murine models of prion disease reducing apoptosis, regulating autophagy and therefore increasing neuronal survival, although TTC did not increase survival time in these models.

Idioma: Inglés

DOI: 10.1007/s12035-021-02489-5

Año: 2021

Publicado en: MOLECULAR NEUROBIOLOGY 58 (2021), 5312–5326
ISSN: 0893-7648

Factor impacto JCR: 5.686 (2021)

Categ. JCR: NEUROSCIENCES rank: 69 / 275 = 0.251 (2021) - Q2 - T1

Factor impacto CITESCORE: 11.0 - Neuroscience (Q1)

Factor impacto SCIMAGO: 1.271 - Neurology (Q1) - Cellular and Molecular Neuroscience (Q1)

Financiación: info:eu-repo/grantAgreement/ES/DGA/A19-20R
Financiación: info:eu-repo/grantAgreement/EUR/FEDER/INTERREG-V-A-POCTEFA-2014-2020

Tipo y forma: Article (Published version)

Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Sanidad Animal (Dpto. Patología Animal)
Área (Departamento): Área Farmacología (Dpto. Farmac.Fisiol.y Med.L.F.)